Mesenchymal Stem Cell Extracellular Vesicles as Adjuvant to Bone Marrow Stimulation in Chondral Defect Repair in a Minipig Model.

OBJECTIVE: This study evaluated the effects of mesenchymal stem cell-extracellular vesicles (MSC-EVs) on chondrocyte proliferation in vitro and on cartilage repair in vivo following bone marrow stimulation (BMS) of focal chondral defects of the knee. METHODS: Six adult Göttingen minipigs received 2 chondral defects in each knee. The pigs were randomized to treatment with either BMS combined with MSC-EVs or BMS combined with phosphate-buffered saline (PBS). Intraarticular injections MSC-EVs or PBS were performed immediately after closure of the surgical incisions, and at 2 and 4 weeks postoperatively. Repair was evaluated after 6 months with gross examination, histology, histomorphometry, immunohistochemistry, and micro-computed tomography (µCT) analysis of the trabecular bone beneath the defect. RESULTS: Defects treated with MSC-EVs had more bone in the cartilage defect area than the PBS-treated defects (7.9% vs. 1.5%, P = 0.02). Less than 1% of the repair tissue in both groups was hyaline cartilage. International Cartilage and Joint Preservation Society II histological scoring showed that defects treated with MSC-EVs scored lower on "matrix staining" (20.8 vs. 50.0, P = 0.03), "cell morphology" (35.4 vs. 53.8, P = 0.04), and "overall assessment" (30.8 vs. 52.9, P = 0.03). Consistently, defects treated with MSC-EVs had lower collagen II and higher collagen I areal deposition. Defects treated with MSC-EVs had subchondral bone with significantly higher tissue mineral densities than PBS-treated defects (860 mg HA/cm3 vs. 838 mg HA/cm3, P = 0.02). CONCLUSION: Intraarticular injections of MSC-EVs in conjunction with BMS led to osseous ingrowth that impaired optimal cartilage repair, while enhancing subchondral bone healing.

Anteromedial Portal Drilling Yielded Better Survivorship of Anterior Cruciate Ligament Reconstructions When Comparing Recent Versus Early Surgeries With This Technique.

PURPOSE: To compare anteromedial (AM) and transtibial (TT) femoral drilling hole techniques in primary anterior cruciate ligament reconstruction, using the Danish Knee Ligament Reconstruction Register, comparing revision rates and clinical outcomes from 2 time periods, 2007 to 2010 and 2012 to 2015. METHODS: A total of 8,386 primary anterior cruciate ligament reconstructions were registered between January 2007 to December 2010 and 8,818 in the period January 2012 to December 2015. Revision ACL was the primary endpoint. Secondary endpoints were the objective and subjective clinical outcomes. Crude and adjusted relative risks (RRs) with 95% confidence interval (CIs) were calculated. RESULTS: The adjusted RR for revision surgery in the AM (2007-10) group compared with the TT (2007-10) group was 1.45 (95% CI, 1.17-1.78; P < .05), but when comparing the AM (2012-15) group with TT (2012-15) group, the RR was 0.99 (95% CI, 0.68-1.45; P = .96). One-year postoperative objective stability testing showed an RR = 1.38 (95% CI, 1.19-1.60; P < .01) for rotational stability and an RR = 1.37 (95% CI, 0.99-1.89; P < .01) for sagittal stability when comparing AM (2007-10) to TT (2007-10). No significant difference in objective stability was found in the more recent period. Lastly, comparing the subjective scores, the AM (2012-15) had a significantly higher Tegner score 1 year postoperatively compared with the TT-group (2012-15). CONCLUSIONS: This study found an increased RR of revision anterior cruciate ligament and rotational and sagittal instability 1 year postoperatively for the AM technique in the period from 2007 to 2010. However, there was no significant difference in revision surgery and objective measures between the techniques from 2012 to 2015. Nevertheless, a higher activity level was found in the AM group. The results could indicate that the results found in the period 2007 to 2010 may have been caused by a learning curve when introducing a new and more complex procedure (AM). LEVEL OF EVIDENCE: Level III, retrospective comparative trial.

Validation of 14,500 operated knees registered in the Danish Knee Ligament Reconstruction Register: registration completeness and validity of key variables.

INTRODUCTION: The aim of this study was to validate the registration in the Danish Knee Ligament Reconstruction Register (DKRR) by assessing the registration completeness of the anterior cruciate ligament (ACL) reconstruction code and detecting the validity of important key variables. Furthermore, we assessed data quality of patient-related outcome scores. MATERIAL AND METHODS: All operation codes for ACL reconstruction from 2005-2011 were identified in the Danish National Registry of Patients and were compared with the cases registered in the DKRR to compute the completeness of registration. We also assessed the validity of key variables in the DKRR using medical records as a reference standard to compute the positive predictive value. Finally, we assessed potential differences between responders and nonresponders to subjective patient-related outcome scores (Knee Injury and Osteoarthritis Outcome Score [KOOS] and Tegner scores) 1 year after surgery. RESULTS: The completeness of the registration of patients in the DKRR increased from 60% (2005) to 86% (2011). Large-volume hospitals had a higher completeness than small-volume hospitals. With a positive predictive value between 85%-100%, the validity of key variables was good. KOOS scores versus Tegner scores for responders and nonresponders were comparable. CONCLUSION: The results show a good registration of ACL reconstruction procedures in the DKRR, but there is room for improvement mainly at small-volume hospitals. Overall, the validity of the key variables in the DKRR was good and no difference was found in KOOS and Tegner scores for responders versus nonresponders. Therefore, we conclude that the DKRR is a valid source for future research.

Anatomic reconstruction of the posterolateral corner of the knee: a case series with isolated reconstructions in 27 patients.

PURPOSE: This study presents clinical results of a case series of isolated reconstruction of the posterolateral corner (PLC) with a new technique that aims to reconstruct the lateral collateral ligament (LCL), popliteus tendon, and popliteofibular ligament. METHODS: From 1997 to 2005, 27 patients available for follow-up with isolated posterolateral instability were treated with primary reconstruction of the LCL and PLC. The median age was 28 years, and there were 16 male patients. Of the patients, 26% had remaining instability after anterior or posterior cruciate ligament reconstruction. All underwent reconstruction with a novel technique addressing both the LCL and the PLC by use of hamstring autografts. Follow-up was more than 24 months, and patients were examined by an independent observer using the International Knee Documentation Committee objective measures and subjective Knee Injury and Osteoarthritis Outcome Scores. RESULTS: In our series 95% of patients with isolated lateral rotatory instability had rotatory stability after PLC reconstruction. On the basis of International Knee Documentation Committee scoring, 71% were normal or nearly normal. Subjective Knee Injury and Osteoarthritis Outcome Scores were comparable to scores in patients after meniscectomy. One patient had a deep infection, but none had any peroneal nerve injury. CONCLUSIONS: This case series presents a new method for combined reconstruction of the LCL and the PLC. Despite the extensiveness of procedure, complications were low. The technique restores lateral stability clinically at 2 years' follow-up. LEVEL OF EVIDENCE: Level IV, therapeutic case series.